Abstract

Atherosclerosis (AS), a leading cause of cardiovascular disease (CVD), is closely associated with excessive oxidative stress. Dietary nitrate has emerged as a promising intervention for cardiovascular protection through the nitrate–nitrite–nitric oxide (NO) pathway. Meanwhile, dental pulp stem cell (DPSC) possess potent antioxidant properties. However, the potential synergistic effect of sodium nitrate (NaNO3) and DPSC on AS remains unclear. In this study, ApoE−/− mice were fed a high‐fat diet (HFD) and treated with NaNO3 and/or DPSC. The combined treatment markedly attenuated atherosclerotic plaque formation, reduced oxidative stress, increased endothelial NO synthase (eNOS) expression, and decreased circulating monocyte levels. Furthermore, in vitro assays revealed that NaNO3 and DPSC synergistically alleviated oxidative stress and promoted macrophage polarization toward the M2 phenotype, thereby suppressing oxidized lipid uptake. Mechanistic studies revealed that these benefits were mediated by activation of the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and the subsequent upregulation of heme oxygenase‐1 (HO‐1). Collectively, our findings unveil a novel therapeutic strategy that combines NaNO3 with DPSC to alleviate oxidative stress and inflammation, presenting a promising approach for the treatment of AS.